Potassium channels play an important role in membrane potential. Among the different types of potassium channels are the ATP-sensitive (K.sub.ATP -) channels which are regulated by changes in the intracellular concentration of adenosine triphosphate. The K.sub.ATP -channels have been found in cells from various tissues such as cardiac cells, pancreatic cells, skeletal muscles, smooth muscles, central neurons and adenohypophysis cells. The channels have been associated with diverse cellular functions for example hormone secretion (insulin from pancreatic beta-cells, growth hormone and prolactin from adenohypophysis cells), vasodilation (in smooth muscle cells), cardiac action potential duration, neurotransmifter release in the central nervous system.
Modulators of the K.sub.ATP -channels have been found to be of importance for the treatment of various diseases. Certain sulphonylureas which have been used for the treatment of non-insulin-dependent diabetes mellitus act by stimulating insulin release through an inhibition of the K.sub.ATP -channels on pancreatic beta-cells.
The potassium channel openers, which comprise a heterogeneous group of compounds, have been found to be able to relax vascular smooth muscles and have therefore been used for the treatment of hypertension.
In addition, potassium channel openers can be used as bronchodilators in the treatment of asthma and various other diseases.
Furthermore, potassium channel openers have been shown to promote hairgrowth, and have been used for the treatment of baldness.
Potassium channel openers are also able to relax urinary bladder smooth muscle and therefore, can be used for the treatment of urinary incontinence. Potassium channel openers which relax smooth muscle of the uterus can be used for treatment of premature labor.
By acting on potassium channels of the central nervous system these compounds can be used for treatment of various neurological and psychiatric diseases such as Alzheimer, epilepsia and cerebral ischemia.
Further, the compounds are found to be useful in the treatment of benign prostatic hyperplasia, erectile dysfunction and in contraception.
Compounds of the present invention, which inhibit insulin secretion by activating potassium channels of the beta-cell can be used in combination with compounds which reduce blood glucose levels. Examples of such compounds are insulin, insulin sensitizers, such as thiazolidinediones, insulin secretagogues, such as repaglinide, tolbutamide, glibenclamide and glucagon like peptide (GLP1), inhibitors of .alpha.-glucosidases and hepatic enzymes responsible for the biosynthesis of glucose, and glucagon.
Recently, it has been shown that Diazoxide (7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide) and certain 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide derivatives inhibit insulin release by an activation of K.sub.ATP -channels on pancreatic beta-cells (Pirotte B. et al. Biochem. Pharmacol, 47, 1381-1386 (1994); Pirotte B. et al., J. Med. Chem., 36, 3211-3213 (1993). Diazoxide has furthermore been shown to delay the onset of diabetes in BB-rats (Vlahos W D et al. Metabolism 40, 39-46 (1991). In obese zucker rats diazoxide has been shown to decrease insulin secretion and increase insulin receptor binding and consequently improve glucose tolerance and decrease weight gain (Alemzadeh R. et al. Endocrinol. 133, 705-712, 1993). It is expected that compounds which activate K.sub.ATP -channels can be used for treatment of diseases characterised by an overproduction of insulin and for the treatment and prevention of diabetes.
The following compounds are known from the literature:
3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-isobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (2-ethylhexylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 cyclohexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-(1,2,2-trimethylpropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-(1,2-dimethylpropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-(1-methylpropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-chloro-3-cyclohexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-chloro-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-dichloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-dichloro-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-isobutylamino-7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-cyclopentylamino-7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-cyclohexylamino-6-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (N-cyclohexyl-N-methylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-cyclohexylamino-4-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-cyclohexylamino-2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide. PA1 R.sup.1 and R.sup.5 independently can be hydrogen; hydroxy; C.sub.1-6 -alkoxy; C.sub.3-6 -cycloalkyl optionally mono- or polysubstituted with C.sub.1-6 -alkyl, halogen, hydroxy or C.sub.1-6 -alkoxy; or C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl or C.sub.2-4 -alkynyl optionally mono- or polysubstituted with halogen and R.sup.4 is hydrogen; or PA1 R.sup.4 together with R.sup.5 represent one of the bonds in a double bond between the atoms 2 and 3 of formula I and R.sup.1 is as defined above; or PA1 R.sup.4 together with R.sup.1 represent one of the bonds in a double bond between the atoms 3 and 4 of formula I and R.sup.5 is as defined above; PA1 D represents --S(.dbd.O).sub.2 -- or --S(.dbd.O)--; PA1 R.sup.2 is hydrogen; hydroxy; C.sub.1-6 -alkoxy; C.sub.3-6 -cycloalkyl optionally mono- or polysubstituted with C.sub.1-6 -alkyl, halogen, hydroxy or C.sub.1-6 -alkoxy; or C.sub.1-6 -alkyl, C.sub.2-6 -alkenyl or C.sub.2-6 -alkynyl optionally mono- or polysubstituted with halogen; PA1 R.sup.3 is R.sup.8 ; --OR.sup.8 ; --C(.dbd.X.sup.1)R.sup.8 ; bicycloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl optionally mono- or polysubstituted with halogen, hydroxy, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, aryloxy, arylalkoxy, nitro, amino, C.sub.1-6 -monoalkyl- or dialkylamino, cyano, oxo, acyl or C.sub.1-6 -alkoxycarbonyl; PA1 wherein R.sup.8 is hydrogen; C.sub.3-6 -cycloalkyl or (C.sub.3-6 -cycloalkyl)C.sub.1-6 -alkyl the C.sub.3-6 -cycloalkyl group optionally being mono- or polysubstituted with C.sub.1-6 -alkyl, halogen, hydroxy or C.sub.1-6 -alkoxy; a 3-6 membered saturated ring system comprising one or more nitrogen-, oxygen- or sulfur atoms, optionally being mono- or polysubstituted with halogen, cyano, trifluoromethyl, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkoxy-C.sub.1-6 -alkyl, aryl, arylalkyl, hydroxy, oxo, nitro, amino, C.sub.1-6 -monoalkyl or dialkylamino; or straight or branched C.sub.1-8 -alkyl optionally mono- or polysubstituted with halogen, hydroxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, C.sub.3-6 -cycloalkyl, aryl, aryloxy, arylalkoxy, nitro, amino, C.sub.1-6 -monoalkyl- or dialkylamino, cyano, oxo, formyl, acyl, carboxy, C.sub.1-6 -alkoxycarbonyl, carbamoyl, formylamino, or C.sub.1-6 -alkylcarbonylamino; PA1 X.sup.1 is O or S; PA1 R.sup.3 is ##STR3## PA1 R.sup.12, R.sup.13, R.sup.14, R.sup.15 independently are hydrogen; halogen; C.sub.1-18 -alkyl; C.sub.3-6 -cycloalkyl; hydroxy; C.sub.1-6 -alkoxy; C.sub.1-6 -alkoxy-C.sub.1-6 -alkyl; nitro; amino; cyano; cyanomethyl; perhalomethyl; C.sub.1-6 -monoalkyl- or dialkylamino; sulfamoyl; C.sub.1-6 -alkylthio; C.sub.1-6 -alkylsulfonyl; C.sub.1-6 -alkylsulfinyl; C.sub.1-6 -alkylcarbonylamino; formyl; arylthio, arylsulfinyl, arylsulfonyl, the aryl group optionally being mono- or polysubstituted with C.sub.1-6 -alkyl, halogen, hydroxy or C.sub.1-6 -alkoxy; C.sub.1-6 -alkoxycarbonyl; C.sub.1-6 -alkoxycarbonyl-C.sub.1-6 -alkyl; carbamyl; carbamylmethyl; C.sub.1-6 -monoalkyl- or dialkylaminocarbonyl; C.sub.1-6 -monoalkyl- or dialkylaminothiocarbonyl; ureido; C.sub.1-6 -monoalkyl- or dialkylaminocarbonylamino, thioureido; C.sub.1-6 -monoalkyl- or dialkylaminothiocarbonylamino; C.sub.1-6 -monoalkyl- or dialkylaminosulfonyl; carboxy; carboxy-C.sub.1-6 -alkyl; acyl; aryl, arylalkyl, aryloxy, the aryl group optionally being mono- or polysubstituted with C.sub.1-6 -alkyl, halogen, hydroxy or C.sub.1-6 alkoxy; (1,2,4-oxadiazol-5-yl)- or (1,2,4-oxadiazol-3-yl)-C.sub.1-6 -alkyl the oxadiazolyl group optionally being substituted with C.sub.1-6 -alkyl or C.sub.3-6 -cycloalkyl; or a 5-6 membered nitrogen containing ring, optionally substituted with phenyl or C.sub.1-6 -alkyl; PA1 3-Benzyloxyamino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-methoxyamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(N-ethyl-N-methylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-methoxyamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(1,2,2-trimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-(1,2,2-trimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(N-ethyl-N-methylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5-Amino-7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(1,3-dimethylpentyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(1,5-dimethylhexyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(1,4-dimethylpentyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5,7-Dichloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-6-trifluoromethyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(3,3-diphenylpropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(4-phenylbutylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(3-diethylamino-1-methylpropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-4H-1,2,4-benzothiadiazine-5-carboxaldehyde 1,1-dioxide PA1 3-Isopropylamino-4H-1,2,4-benzothiadiazine-7-carboxaldehyde 1,1-dioxide PA1 3-Isopropylamino-4H-1,2,4-benzothiadiazine-6-carboxylic acid 1,1-dioxide PA1 7-Cyano-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-7-iodo-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-cyanomethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5,7-Dichloro-3-isopropylamino-6-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(3-(1H-imidazol-4-yl)propyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6,7-dimethoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(1-Azabicyclo[2.2.2]oct-3-yl)amino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(1,2-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(1,2-dimethylpropyl)amino-7-sulfamoyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Anilino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(imidazol-2-yl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(4-pyridyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-isobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-6-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-cyclohexylmethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopentylamino-6-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-isopropylamino-5-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-tert-Butylamino-6-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Iodo-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-7-fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-cyclopropylmethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5,7-Dibromo-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Acetyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Allylamino-6-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(1-ethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-butylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-hexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(1,2-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(1-methylbutyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(1,2-dimethylpropyl)amino-2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-isopropylamino-2-methyl-2H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6-benzenesulfonyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6-methanesulfonyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5-Chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-isopropylamino-7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Ethoxycarbonylmethyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Carboxymethyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 8-Chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Isopropyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-tert-Butyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-6-phenoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Hexyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Cyclohexyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 2-(3-Isopropylamino-1,1-dioxo-1,4-dihydro-1.lambda..sup. 6,2,4-benzothiadiazin-6-yl)-acetamide PA1 6-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)methyl-3-isopropylamino-4H-1,2,4-benz othiadiazine 1,1-dioxide PA1 6-Cyanomethyl-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-phenylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Iodo-3-(1,2-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Iodo-3-(1,2,2-trimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-cyclohexylmethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (R)-7-Chloro-3-(1-cyclohexylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (S)-7-Chloro-3-(1-cyclohexylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (R)-7-Chloro-3-(1-phenylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (S)-7-Chloro-3-(1-phenylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclohexyimethylamino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (R)-3-(1-Cyclohexylethyl)amino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (S)-3-(1-Cyclohexylethyl)amino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Benzyiamino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (R)-7-Iodo-3-(1-phenylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 (S)-7-Iodo-3-(1-phenylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-7-bromo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-(1,2-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(1,2-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2,2,2-trifluoroethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-7-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Allylamino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-methoxy-1-methylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(1-ethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(1-Ethylpropyl)amino-7-iodo-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-7-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(1,2-Dimethylpropyl)amino-7-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-hydroxypropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-hydroxy-1-methylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(2-Aminoethyl)amino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2,2-diethoxyethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Ethylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopropylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclobutylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopentylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopropylmethylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Allylamino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(2-methoxy-1-methylethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(2,2,2-trifluoroethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-(2,2,2-trifluoroethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-hexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-hexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(2,2-Diethoxyethyl)amino-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(2,2,2-trifluoroethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Bromo-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-cyclopropylmethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopropylmethylamino-7-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Nitro-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclobutylamino-7-nitro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Amino-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Acetamido-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclobutylamino-7-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Methoxy-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-formylaminoethyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-(2-Acetylaminoethyl)amino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5-Chloro-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5-Chloro-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 5-Chloro-3-hexylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-octylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(1,5-dimethylhexyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-sec-Butylamino-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Isopropylamino-4H-1,2,4-benzothiadiazine-7-carboxylic acid 1,1-dioxide PA1 3-sec-Butylamino-4H-1,2,4-benzothiadiazine-7-carboxylic acid 1,1-dioxide PA1 3-Propylamino-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Cyclopropylmethylamino-7-trifluoromethyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Propylamino-4H-1,2,4-benzothiadiazine-7-carboxylic acid 1,1-dioxide PA1 7-Chloro-3-(pyridin-2-yl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 3-Ethylamino-6,7-difluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3,6-di(isopropylamino)-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7,8-Trifluoro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-isopropylamino-6-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-isopropylamino-6-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-cyclopropylmethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-cyclopentylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Chloro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Chloro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 7-Fluoro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6-Fluoro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Dichloro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Dichloro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,7-Difluoro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(2-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(3-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(4-pyridyl)methylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(2-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(3-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Difluoro-3-(4-pyridyl)ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-(1,4-dimethylpentyl)amino-4H-1,2,4-benzothiadiaz ine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-cyclopentylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-cyclopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-propylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6,8-Bis(trifluoromethyl)-3-cyclobutylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 6.8-Bis(trifluoromethyl)-3-ethylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide PA1 a) reacting a compound of formula II: ##STR4## PA1 b) reacting a compound of formula IV: ##STR6## PA1 c) reacting a compound of the formula IV: ##STR7## PA1 d) reacting a compound of formula V ##STR8## PA1 e) reacting a compound of the formula V ##STR9## PA1 f) reacting a compound of the formula V ##STR10## PA1 g) reacting a compound of the formula V ##STR12## PA1 h) reacting in the presence of a base a compound of formula X ##STR13## PA1 i) hydrolyzing and subsequently decarboxylating a compound of the general formula XIII ##STR16## PA1 j) reacting a compound of formula ##STR17##